In this renewal application, we propose to investigate three major Specific Aims in relation to melanoma staging. Aim 1. Determine whether methods which were developed at the JWCI for identifying patients with clinical Stage I melanoma who have micrometastases to regional nodes and may benefit from regional lymphadenectomy, can be confirmed in a multicenter trial. at other institutions. Aim 2. Develop methods for identifying patients who have micrometastases at a systemic site based upon serum markers for subclinical disease. Aim 3. Determine whether the concepts developed for improved stating of melanoma can be applied to other neoplasms. Immunological, histological and surgical techniques will be utilized. Approaches to investigate Aim #1 include: a) Characterize the nature of the primary melanoma which indicates the metastasizing phenotype; b) Intraoperative lymphatic mapping and selective lymphadenectomy before radical lymphadenectomy. Approaches to investigate Aim #2 include: a) Characterize the melanoma found in lymph nodes for those patients who are destined to develop recurrences; b) Use of specific immune markers which indicate prognosis at over 80% accuracy; and c) Detect patients with distant metastases within Stage I melanoma by immunologic techniques. Approaches to investigate Aim #3 include: a) Develop methods to accurately determine the presence of micrometastases in the regional nodes of neoplasms other than melanoma such as breast or lung cancer. The primary objective of this project is to develop new approaches to the surgical management of primary cutaneous melanoma and other types of solid neoplasms. We hope to develop new criteria for surgical therapy which will identify patients in need of adjuvant therapy and differentiate these from patients in whom surgical therapy alone is curative. The sole criteria being used by many oncologists for their determination of therapy modality is the size of the primary neoplasm and the extend of clinically detectable disease. However, existing therapy could be improved if accurate techniques to detect micrometastases are developed.